Molecular Playground/TRAIL

One of the CBI Molecules being studied in the University of Massachusetts Amherst Chemistry-Biology Interface Program at UMass Amherst and on display at the Molecular Playground.



TRAIL

Molecular Playground Banner: TRAIL, a novel cancer therapeutic

TRAIL, or tumor-necrosis factor apoptosis-inducing ligand, is a member of the TNF superfamily that has attracted attention for its specificity towards cancer cells with limited toxicity towards most normal cells. TRAIL is a type II transmembrane protein with an extracellular domain that can be proteolyticly cleaved, and which forms a homotrimer that binds three monomeric death receptors (DRs). It binds to DR4 and DR5, which elicit signal transduction of caspase-8 mediated apoptosis via the death receptor pathway, or it can bind to the decoy receptors (DcR1, DcR2, or osteoprotegerin) which have truncated or non-functional intracellular death domains. Receptor binding by TNFα can stimulate both pro-apoptotic signals (via caspase-8) and anti-apoptotic signals (via NFκB). However, TRAIL has attenuated induction of NFκB, leading to a pronounced death signal via a p53-independent mechanism. In addition, the antagonistic decoy receptors are widely-expressed in normal tissues and confer a resistance to TRAIL-mediated apoptosis.

This scene shows only the extracellular domain of TRAIL. Each beta-sheet is shown in a different color and the bright green loop designates the section of the protein which is responsible for binding with the various death receptors.